Clinical pharmacokinetics of adefovir in human immunodeficiency virus type 1-infected patients

K. C. Cundy, P. Barditch-Crovo, R. E. Walker, A. C. Collier, D. Ebeling, J. Toole, H. S. Jaffe

Research output: Contribution to journalArticle

Abstract

The pharmacokinetics and bioavailability of adefovir [9-[2- (phosphonomethoxy)ethyl]adenine] were examined at two dose levels in three phase I/II studies in 28 human immunodeficiency type 1-infected patients. The concentrations of adefovir in serum following the intravenous infusion of 1.0 or 3.0 mg/kg of body weight were dose proportional and declined biexponentially, with an overall mean ± standard deviation terminal half- life of 1.6 ± 0.5 h (n = 28). Approximately 90% of the intravenous dose was recovered unchanged in the urine in 12 h, and more than 98% was recovered by 24 h postdosing. The overall mean ± standard deviation total serum clearance of the drug (223 ± 53 ml/h/kg; n = 25) approximated the renal clearance (205 ± 78 ml/h/kg; n = 20), which was significantly higher (P < 0.01) than the baseline creatinine clearance in the same patients (88 ± 18 ml/h/kg; n = 25). Since adefovir is essentially completely unbound in plasma or serum, these data indicate that active tubular secretion accounted for approximately 60% of the clearance of adefovir. The steady-state volume of distribution of adefovir (418 ± 76 ml/kg; n = 28) suggests that the drug was distributed in total body water. Repeated daily dosing with adefovir at 1.0 mg/kg/day (n = 8) and 3.0 mg/kg/day (n = 4) for 22 days did not significantly alter the pharmacokinetics of the drug; there was no evidence of accumulation. The oral bioavailability of adefovir at a 3.0.mg/kg dose was <12% (n = 5) on the basis of the concentrations in serum or 16.4% ± 16.0% on the basis of urinary recovery. The subcutaneous bioavailability of adefovir at a 3.0-mg/kg dose was 102% ± 8.3% (n = 5) on the basis of concentrations in serum or 84.8% ± 28.5% on the basis of urinary recovery. These data are consistent with preclinical observations in various species.

Original languageEnglish (US)
Pages (from-to)2401-2405
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume39
Issue number11
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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  • Cite this

    Cundy, K. C., Barditch-Crovo, P., Walker, R. E., Collier, A. C., Ebeling, D., Toole, J., & Jaffe, H. S. (1995). Clinical pharmacokinetics of adefovir in human immunodeficiency virus type 1-infected patients. Antimicrobial agents and chemotherapy, 39(11), 2401-2405. https://doi.org/10.1128/AAC.39.11.2401